tbuckley/cabot-search huggingface dataset:
A Strategy of Fenton Reaction Cycloacceleration for High‐Performance Ferroptosis Therapy Initiated by Tumor Microenvironment Remodeling
Authors: Lin Huang, Jie Feng, Jiaoyang Zhu, Jing Yang, Wei Xiong, Xuanyi Lu, Sijin Chen, Sugeun Yang, Yan Li, Yikai Xu, Zheyu Shen
Journal: Advanced Healthcare Materials (2023)

Abstract The emerging tumor ferroptosis therapy confronts impediments of the tumor microenvironment (TME) with weak intrinsic acidity, inadequate endogenous H 2 O 2 , and a powerful intracellular redox balance system that eliminates toxic reactive oxygen species (ROS). Herein, a strategy of Fenton reaction cycloacceleration initiated by remodeling the TME for magnetic resonance imaging (MRI)‐guided high‐performance ferroptosis therapy of tumors is proposed. The synthesized nanocomplex exhibits enhanced accumulation at carbonic anhydrase IX (CAIX)‐positive tumors based on the CAIX‐mediated active targeting, and increased acidification via the inhibition of CAIX by 4‐(2‐aminoethyl) benzene sulfonamide (ABS) (remodeling TME). This accumulated H + and abundant glutathione in TME synergistically trigger biodegradation of the nanocomplex to release the loaded cuprous oxide nanodots (CON), β ‐lapachon (LAP), Fe 3+ , and gallic acid‐ferric ions coordination networks (GF). The Fenton and Fenton‐like reactions are cycloaccelerated via the catalytic loop of Fe‐Cu, and the LAP‐triggered and nicotinamide adenine dinucleotide phosphate quinone oxidoreductase1‐mediated redox cycle, generating robust ROS and plenitudinous lipid peroxides accumulation for ferroptosis of tumor cells. The detached GF network has improved relaxivities in response to the TME. Therefore, the strategy of Fenton reaction cycloacceleration initiated by remodeling the TME is promising for MRI‐guided high‐performance ferroptosis therapy of tumors.
Precutting and trimming-assisted underwater endoscopic mucosal resection for large early esophageal cancer
Authors: Chao Deng, Suhua Wu, Feng Xu, Zhihang Zhou, Yunjia Zhu, Zhechuan Mei, Song He
Journal: Endoscopy (2023)

A 72-year-old man was diagnosed with early esophageal cancer and underwent endoscopic resection. After marking the lesion, the size was about 4.0 × 3.0 cm. After submucosal injection, mucosal incision was performed with Endocut Q (Effect 3, Cut duration 2, Cut interval 4), followed by the trimming of the edges with swift coagulation (Effect 3, 45 W), the so-called precutting and trimming technique ([Fig. 1 a]). Because the marginal mucosa had been fully incised, under the condition of continuous water injection, the lesion floated in the water, which allowed it to be completely snared and removed using a 30-mm snare ([Fig. 1 b]). No residual lesion, bleeding, or perforation was observed on the wound ([Fig. 1 c]). The whole operation lasted 20 minutes. Iodine staining after the specimen was stretched and fixed confirmed the presence of all the marks and the size of 4.2 × 3.0 cm ([Fig. 1 d]). The histological findings revealed pathological lamina propria (pT1a-LPM) squamous cell carcinoma with negative horizontal and vertical margins.
The need for appropriate language in the debate on medicalisation of pregnancy
Authors: Catherine Cluver, Christianne de Groot, Ben W Mol, Kellie E Murphy, Jane E Norman, Rodolfo Pacagnella, Kirsten Palmer, Liona C Poon, Daniel L Rolnik, Catherine Y Spong, Sarah J Stock, Shakila Thangaratinam, Stephen Tong, Corine Verhoeven, Lan N Vuong, Sue P Walker, Liu Xiaohua
Journal: The Lancet (2023)
Endoscopic ultrasonography successfully diagnosed pancreas divisum and santorinicele
Authors: Qingyun He, Rui Xie, Xu Li, Shuwen Han, Guoqing Shi, Biguang Tuo, Huichao Wu
Journal: Endoscopy (2023)

Corrected by: Correction: Endoscopic ultrasonography successfully diagnosed pancreas divisum and santoriniceleEndoscopy 2023; 55(S 01): C2-C2DOI: 10.1055/a-2053-3119
Recent advances in CRISPR-based genome editing technology and its applications in cardiovascular research
Authors: Zhen-Hua Li, Jun Wang, Jing-Ping Xu, Jian Wang, Xiao Yang
Journal: Military Medical Research (2023)

Abstract The rapid development of genome editing technology has brought major breakthroughs in the fields of life science and medicine. In recent years, the clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing toolbox has been greatly expanded, not only with emerging CRISPR-associated protein (Cas) nucleases, but also novel applications through combination with diverse effectors. Recently, transposon-associated programmable RNA-guided genome editing systems have been uncovered, adding myriads of potential new tools to the genome editing toolbox. CRISPR-based genome editing technology has also revolutionized cardiovascular research. Here we first summarize the advances involving newly identified Cas orthologs, engineered variants and novel genome editing systems, and then discuss the applications of the CRISPR-Cas systems in precise genome editing, such as base editing and prime editing. We also highlight recent progress in cardiovascular research using CRISPR-based genome editing technologies, including the generation of genetically modified in vitro and animal models of cardiovascular diseases (CVD) as well as the applications in treating different types of CVD. Finally, the current limitations and future prospects of genome editing technologies are discussed.
Endoscopic laser lithotripsy for a giant duodenal bezoar: the first clinical experience
Authors: Xiao-Peng Zhang, Qing-Fen Zheng, Li-Xia Zhao, De-Liang Li, Dan Liu, Xie-Fu Zhang, Bing-Rong Liu
Journal: Endoscopy (2023)

A bezoar causing complete duodenal obstruction is uncommon; surgical operation is the usual treatment choice when it does occur. Here, we report our experience of using endoscopic laser lithotripsy for a giant duodenal bezoar.
Endoscopic ultrasound-guided colocolostomy for malignant transverse colon obstruction after failure of enteral stenting
Authors: Muhan Ni, Shanshan Shen, Bin Zhang, Lei Wang
Journal: Endoscopy (2023)

Developments in therapeutic endoscopic ultrasound (EUS) have allowed the endoscopic creation of gastrointestinal anastomoses for gastric outlet obstruction [1] [2]. However, this approach is rarely performed for the lower gastrointestinal tract because of the technical challenge of EUS-guided colocolostomy. Herein, we describe EUS-guided colocolostomy in a patient with malignant obstruction affecting a long segment of the transverse colon after failure of enteral stenting.
Closure of a large post-endoscopic submucosal dissection mucosal defect in the duodenum with a novel through-the-scope twin clip
Authors: Mingyang Ma, Siying Liu, Jiewei Wang, Peng Li, Shutian Zhang
Journal: Endoscopy (2023)

The European Society of Gastrointestinal Endoscopy recommends routine clip closure for defects ≤ 20 mm following duodenal endoscopic mucosal resection or endoscopic submucosal dissection (ESD) [1]. However, large resection sites that cannot be fully closed by this kind of clip are associated with higher adverse event rates [2]. A through-the-scope twin clip (TTS-TC) can close large wounds with a size of up to 4.8 cm via an endoscope working channel of 3.2 mm [3]. We present an initial application of TTS-TC for closure of a large duodenal mucosal defect ([Video 1]).
Curative en bloc resection of a laterally spreading mixed-nodular papillary tumor with endoscopic submucosal dissection: a case report
Authors: Shuhan Yu, Ting Zhang, Lijuan Mao, Zeyu Wu, Qide Zhang
Journal: Endoscopy (2023)

A 56-year-old man was referred to our hospital with epigastric pain for 3 months. A white light image revealed a laterally spreading mixed-nodular tumor at the duodenal major papilla ([Fig. 1]), diagnosed as a tubular adenoma by biopsy. Narrow-band imaging with magnifying endoscopy demonstrated distinct demarcation, irregular micro-vessel plus surface pattern, and positive white opaque substance (WOS). After signed informed consent, we performed endoscopic submucosal dissection (ESD) using dental floss traction with a supine position ([Video 1]) and captured a resection specimen of 30 × 35 mm ([Fig. 2]).
Complete sealing of a duodenal perforation during endoscopic submucosal dissection using a novel through-the-scope twin clip
Authors: Xianzong Ma, Lang Yang, Dongliang Yu, Jie Zhang, Zilin Kang, Peng Jin
Journal: Endoscopy (2023)

Intraprocedure and postprocedure perforation are serious complications that limit the clinical application of endoscopic submucosal dissection (ESD) for duodenal neoplasia; thus, how to seal a perforation of the duodenum during ESD efficiently and safely is an important topic. Current sealing instruments include conventional through-the-scope (TTS) clips with or without nylon purse-string sutures, over-the-scope (OTS) clips, and high-end suture devices; however, these are time-consuming, high-cost, and difficult to use for sealing large perforations [1] [2]. We report the successful application of a novel TTS twin clip (TTS-TC), which is expected to achieve efficient closure of large perforations in difficult locations, in sealing a duodenal perforation that occurred during ESD [1] [3] [4] [5].
Underwater endoscopic mucosal resection using a detachable snare for a pedunculated lesion located in the greater curvature of the upper gastric body
Authors: Shogo Nakano, Hiroyoshi Iwagami, Yoshiki Morihisa, Takafumi Konishi, Yasuki Nakatani, Takuji Akamatsu, Yukitaka Yamashita
Journal: Endoscopy (2023)

The usefulness of underwater endoscopic mucosal resection (UEMR) has been shown for colorectal and duodenal lesions [1] [2] as well as gastric lesions, especially those located in the greater curvature of the gastric body [3] [4]. As it is difficult to approach and dissect such gastric lesions using endoscopic submucosal dissection, UEMR is sometimes chosen as an alternative treatment.
Risk-Stratified Screening for Colorectal Cancer Using Genetic and Environmental Risk Factors: A Cost-Effectiveness Analysis Based on Real-World Data
Authors: Rosita van den Puttelaar, Reinier G.S. Meester, Elisabeth F.P. Peterse, Ann G. Zauber, Jiayin Zheng, Richard B. Hayes, Yu-Ru Su, Jeffrey K. Lee, Minta Thomas, Lori C. Sakoda, Yi Li, Douglas A. Corley, Ulrike Peters, Li Hsu, Iris Lansdorp-Vogelaar
Journal: Clinical Gastroenterology and Hepatology (2023)

Previous studies on the cost-effectiveness of personalized colorectal cancer (CRC) screening were based on hypothetical performance of CRC risk prediction and did not consider the association with competing causes of death. In this study, we estimated the cost-effectiveness of risk-stratified screening using real-world data for CRC risk and competing causes of death.
Identifying, Understanding, and Managing Fecal Urgency in Inflammatory Bowel Diseases
Authors: Bénédicte Caron, Subrata Ghosh, Silvio Danese, Laurent Peyrin-Biroulet
Journal: Clinical Gastroenterology and Hepatology (2023)

Fecal urgency, which is defined by the sudden need to rush to the bathroom to empty one's bowel, is one of the common and distressing symptoms experienced by patients with inflammatory bowel disease.We performed a narrative review to investigate the definition, pathophysiology, and therapeutic management of fecal urgency.Definitions of fecal urgency in inflammatory bowel disease, but also in irritable bowel syndrome, oncology, nononcologic surgery, obstetrics and gynecology, and in proctology, are empirical and heterogenous, lacking standardization. In the majority of these studies, nonvalidated questionnaires were used. When nonpharmacologic measures (dietary regimen, cognitive behavioral program) fail, medications such as loperamide, tricyclic antidepressants, or biofeedback therapy may become necessary. Medical management of fecal urgency may be challenging, in part because only limited data are available regarding the treatment of this symptom in randomized clinical trials of biologics in patients with inflammatory bowel disease.There is an urgent need for a systematic approach to assessment of fecal urgency in inflammatory bowel disease. It is time to consider fecal urgency as an outcome in clinical trials to remedy this disabling symptom.
MYC determines lineage commitment in KRAS-driven primary liver cancer development
Authors: Luana D’Artista, Athina Anastasia Moschopoulou, Iros Barozzi, Amanda J. Craig, Marco Seehawer, Lea Herrmann, Martina Minnich, Tae-Won Kang, Elke Rist, Melanie Henning, Sabrina Klotz, Florian Heinzmann, Jule Harbig, Bence Sipos, Thomas Longerich, Martin Eilers, Daniel Dauch, Johannes Zuber, Xin Wei Wang, Lars Zender
Journal: Journal of Hepatology (2023)

Primary liver cancer (PLC) comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), two frequent and lethal tumour types that differ regarding their tumour biology and responses to cancer therapies. Liver cells harbour a high degree of cellular plasticity and can give rise to either HCC or iCCA. However, little is known about the cell-intrinsic mechanisms directing an oncogenically transformed liver cell to either HCC or iCCA. The scope of this study was to identify cell-intrinsic factors determining lineage commitment in PLC.
Tom Nolan’s research reviews—9 March 2023
Authors: Tom Nolan
Journal: BMJ (2023)

The eight survival secretsEat better, be more active, quit tobacco, get healthy sleep, manage weight, control cholesterol, manage blood pressure, and manage blood sugar: the American Heart Association's "Life's Essential 8" sounds a lot like my long abandoned list of New Year's resolutions.A cohort study from the UK Biobank finds that those who manage to adhere to the Essential 8 and have better cardiovascular health live longer: women with high cardiovascular health (according to a score based on the Essential 8) aged 50 years lived 9.4 years longer than women with low cardiovascular health, for instance.That's hardly surprising, but more intriguing is the finding that, among those with a high level of cardiovascular health, there was no difference in disease-free life expectancy between participants with low socioeconomic status and other socioeconomic groups.
Pharmacological disruption of mSWI/SNF complex activity restricts SARS-CoV-2 infection
Authors: Jin Wei, Ajinkya Patil, Clayton K. Collings, Mia Madel Alfajaro, Yu Liang, Wesley L. Cai, Madison S. Strine, Renata B. Filler, Peter C. DeWeirdt, Ruth E. Hanna, Bridget L. Menasche, Arya Ökten, Mario A. Peña-Hernández, Jon Klein, Andrew McNamara, Romel Rosales, Briana L. McGovern, M. Luis Rodriguez, Adolfo García-Sastre, Kris M. White, Yiren Qin, John G. Doench, Qin Yan, Akiko Iwasaki, Thomas P. Zwaka, Jun Qi, Cigall Kadoch, Craig B. Wilen
Journal: Nature Genetics (2023)

Abstract Identification of host determinants of coronavirus infection informs mechanisms of viral pathogenesis and can provide new drug targets. Here we demonstrate that mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) chromatin remodeling complexes, specifically canonical BRG1/BRM-associated factor (cBAF) complexes, promote severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and represent host-directed therapeutic targets. The catalytic activity of SMARCA4 is required for mSWI/SNF-driven chromatin accessibility at the ACE2 locus, ACE2 expression and virus susceptibility. The transcription factors HNF1A/B interact with and recruit mSWI/SNF complexes to ACE2 enhancers, which contain high HNF1A motif density. Notably, small-molecule mSWI/SNF ATPase inhibitors or degraders abrogate angiotensin-converting enzyme 2 (ACE2) expression and confer resistance to SARS-CoV-2 variants and a remdesivir-resistant virus in three cell lines and three primary human cell types, including airway epithelial cells, by up to 5 logs. These data highlight the role of mSWI/SNF complex activities in conferring SARS-CoV-2 susceptibility and identify a potential class of broad-acting antivirals to combat emerging coronaviruses and drug-resistant variants.
Linoleic acid potentiates CD8+ T cell metabolic fitness and antitumor immunity
Authors: Carina B. Nava Lauson, Silvia Tiberti, Paola A. Corsetto, Federica Conte, Punit Tyagi, Markus Machwirth, Stefan Ebert, Alessia Loffreda, Lukas Scheller, Dalia Sheta, Zeinab Mokhtari, Timo Peters, Ayush T. Raman, Francesco Greco, Angela M. Rizzo, Andreas Beilhack, Giovanni Signore, Nicola Tumino, Paola Vacca, Liam A. McDonnell, Andrea Raimondi, Philip D. Greenberg, Johannes B. Huppa, Simone Cardaci, Ignazio Caruana, Simona Rodighiero, Luigi Nezi, Teresa Manzo
Journal: Cell Metabolism (2023)

The metabolic state represents a major hurdle for an effective adoptive T cell therapy (ACT). Indeed, specific lipids can harm CD8+ T cell (CTL) mitochondrial integrity, leading to defective antitumor responses. However, the extent to which lipids can affect the CTL functions and fate remains unexplored. Here, we show that linoleic acid (LA) is a major positive regulator of CTL activity by improving metabolic fitness, preventing exhaustion, and stimulating a memory-like phenotype with superior effector functions. We report that LA treatment enhances the formation of ER-mitochondria contacts (MERC), which in turn promotes calcium (Ca2+) signaling, mitochondrial energetics, and CTL effector functions. As a direct consequence, the antitumor potency of LA-instructed CD8 T cells is superior in vitro and in vivo. We thus propose LA treatment as an ACT potentiator in tumor therapy.
Convergent coexpression of autism-associated genes suggests some novel risk genes may not be detectable in large-scale genetic studies
Authors: Calwing Liao, Mariana Moyses-Oliveira, Celine E.F. De Esch, Riya Bhavsar, Xander Nuttle, Aiqun Li, Alex Yu, Nicholas D. Burt, Serkan Erdin, Jack M. Fu, Minghui Wang, Theodore Morley, Lide Han, Patrick A. Dion, Guy A. Rouleau, Bin Zhang, Kristen J. Brennand, Michael E. Talkowski, Douglas M. Ruderfer
Journal: Cell Genomics (2023)

Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder characterized by deficits in social interactions and communication. Protein-altering variants in many genes have been shown to contribute to ASD; however, understanding the convergence across many genes remains a challenge. We demonstrate that coexpression patterns from 993 human postmortem brains are significantly correlated with the transcriptional consequences of CRISPR perturbations in human neurons. Across 71 ASD risk genes, there was significant tissue-specific convergence implicating synaptic pathways. Tissue-specific convergence was further demonstrated across schizophrenia and atrial fibrillation risk genes. The degree of ASD convergence was significantly correlated with ASD association from rare variation and differential expression in ASD brains. Positively convergent genes showed intolerance to functional mutations and had shorter coding lengths than known risk genes even after removing association with ASD. These results indicate that convergent coexpression can identify potentially novel genes that are unlikely to be discovered by sequencing studies.
Transcriptome analysis reveals tumor microenvironment changes in glioblastoma
Authors: Youri Hoogstrate, Kaspar Draaisma, Santoesha A. Ghisai, Levi van Hijfte, Nastaran Barin, Iris de Heer, Wouter Coppieters, Thierry P.P. van den Bosch, Anne Bolleboom, Zhenyu Gao, Arnaud J.P.E. Vincent, Latifa Karim, Manon Deckers, Martin J.B. Taphoorn, Melissa Kerkhof, Astrid Weyerbrock, Marc Sanson, Ann Hoeben, Slávka Lukacova, Giuseppe Lombardi, Sieger Leenstra, Monique Hanse, Ruth E.M. Fleischeuer, Colin Watts, Nicos Angelopoulos, Thierry Gorlia, Vassilis Golfinopoulos, Vincent Bours, Martin J. van den Bent, Pierre A. Robe, Pim J. French
Journal: Cancer Cell (2023)

A better understanding of transcriptional evolution of IDH-wild-type glioblastoma may be crucial for treatment optimization. Here, we perform RNA sequencing (RNA-seq) (n = 322 test, n = 245 validation) on paired primary-recurrent glioblastoma resections of patients treated with the current standard of care. Transcriptional subtypes form an interconnected continuum in a two-dimensional space. Recurrent tumors show preferential mesenchymal progression. Over time, hallmark glioblastoma genes are not significantly altered. Instead, tumor purity decreases over time and is accompanied by co-increases in neuron and oligodendrocyte marker genes and, independently, tumor-associated macrophages. A decrease is observed in endothelial marker genes. These composition changes are confirmed by single-cell RNA-seq and immunohistochemistry. An extracellular matrix-associated gene set increases at recurrence and bulk, single-cell RNA, and immunohistochemistry indicate it is expressed mainly by pericytes. This signature is associated with significantly worse survival at recurrence. Our data demonstrate that glioblastomas evolve mainly by microenvironment (re-)organization rather than molecular evolution of tumor cells.
Neural knowledge assembly in humans and neural networks
Authors: Stephanie Nelli, Lukas Braun, Tsvetomira Dumbalska, Andrew Saxe, Christopher Summerfield
Journal: Neuron (2023)

Human understanding of the world can change rapidly when new information comes to light, such as when a plot twist occurs in a work of fiction. This flexible "knowledge assembly" requires few-shot reorganization of neural codes for relations among objects and events. However, existing computational theories are largely silent about how this could occur. Here, participants learned a transitive ordering among novel objects within two distinct contexts before exposure to new knowledge that revealed how they were linked. Blood-oxygen-level-dependent (BOLD) signals in dorsal frontoparietal cortical areas revealed that objects were rapidly and dramatically rearranged on the neural manifold after minimal exposure to linking information. We then adapt online stochastic gradient descent to permit similar rapid knowledge assembly in a neural network model.
Children and TB pharmacokinetics: no longer in infancy?
Authors: Justin T. Denholm
Journal: European Respiratory Journal (2023)

The comprehensive report from Gafar et al. [1] in this issue of the European Respiratory Journal provides the first systematic assessment of antituberculosis drug pharmacokinetics in children and adolescents to date. The authors have admirably collected and analysed the available information on this important topic, which also provides an opportunity for considering the gaps which still remain in our understanding and practice. While this approach to synthesis using an individual patient meta-analysis is an important contribution from this team, it is also reflective of the collective efforts of a significant number of smaller and carefully conducted studies over a 25-year period, each with groups willing to curate and share necessary data. This work, then, highlights a wider community of researchers, patients and families who have helped to build a platform on which better treatment can be developed and delivered. Accumulating evidence on TB pharmacokinetics in children and adolescents will be useful for improving outcomes and individualising therapy in future http://bit.ly/3E6hWSP
Central apnoeas, sympathetic activation and mortality in heart failure: look before you leap
Authors: Chiara Borrelli, Jens Spiesshoefer, Vaughan Macefield, Alberto Giannoni
Journal: European Respiratory Journal (2023)

<b>The debate of central apnoea and its treatment in heart failure is very much alive, and measures comprising the effects on sympathetic measures of therapeutic options should be evaluated, albeit with careful consideration</b>https://bit.ly/3EVpXKv